Vascular endothelial growth factor A/vascular permeability factor (VEGF A/VPF) is a complete pro-angiogenic growth factor that increases permeability of microvessels, stimulates endothelial cell proliferation, migration, and differentiation into tubules, which are precursors to blood vessels. In addition, it can also serve as a survival factor that protects vascular endothelial cells against apoptosis and senescence.
Although one gene encodes for rodent and human VEGF-A, a number of VEGF-A proteins with specific activities can be produced through alternative splicing of the eight exons within the single VEGF gene. In humans, seven different alternative splice variants of VEGF have been identified thus far. In the murine system, five alternative splice variants have been identified, which are one amino acid shorter than those in the human system.
The splice variants of murine VEGF thus far identified are designated as VEGF120, VEGF144, VEGF164, and VEGF188. The basis for the different biological functions of VEGF splice variants is based on the specific exons present in the mRNA of the splice variant that determines the amino acids present and in turn determines the differences in the binding and affinity of the VEGF-A splice variants for the VEGF receptors, which include the receptor tyrosine kinases VEGFR-1, VEGFR-2, and the co-receptors, neuropilin-1 (NP-1) and NP-2. Endothelial cell proliferation is stimulation through phosphorylation of VEGFR-2 (Flk-1/KDR).
The existence of a novel VEGF alternative splice transcript was previously reported, and designated VEGF205. That variant was present only in mouse skin papillomas and squamous cell carcinomas, but not in normal skin. In this specification, we describe for the first time the cloning, sequencing, and characterization of a new VEGF, VEGF205*, a 145-amino acid protein with significantly different carboxyl-terminus tail than any other VEGF alternative splice variant described to date in mouse or human systems.